GKT137831
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Ki值:140 nM和110 nM
GKT137831是特异性的NADPH氧化酶Nox1/Nox4双重抑制剂[1].
Nox1和Nox4均在血管平滑肌细胞(VSMC)中表达,但位于细胞内的不同部位,分别受生长因子和血管损伤的调控,并通过不同机制被激活.
体外:GKT137831可在HPAECs和HPASMCs中降低低氧诱导的H(2)O(2)释放\细胞增殖和TGF-β1表达,并可衰减PPARγ的减少.[2] 在人类主动脉内皮细胞中,GKT137831也可阻断响应高血糖的氧化应激.[3]
体内:在WT和SOD1突变小鼠中,GKT137831(60 mg/kg i.g.)可防止肝纤维化,并可下调氧化应激\炎症和纤维化的标记物.[1]在慢性低氧暴露的小鼠模型中,GKT137831(60 mg/kg/d p.o.)可衰减肺中PPARγ和TGF-β1的表达,并衰减慢性低氧诱导的右心室肥大\血管重构\肺细胞增殖和低氧变化[2].GKT137831(60 mg/kg/d p.o.)也可在糖尿病载脂蛋白E缺陷小鼠中衰减糖尿病刺激的动脉粥样硬化.[3]并且,GKT137831可预防血管紧张素Ⅱ灌注的c-hNox4Tg小鼠的氧化应激增加,废除Akt-mTOR和NF-κB信号通路,减少心脏重塑.[4]临床试验:临床研究未进行.
参考文献:
[1] Aoyama T, Paik YH, Watanabe S, Laleu B, Gaggini F, Fioraso-Cartier L, Molango S, Heitz F, Merlot C, Szyndralewiez C, Page P, Brenner DA. Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent. Hepatology. 2012 Dec;56(6):2316-27.
[2] Green DE, Murphy TC, Kang BY, Kleinhenz JM, Szyndralewiez C, Page P, Sutliff RL, Hart CM. Circulation. The Nox4 inhibitor GKT137831 attenuates hypoxia-induced pulmonary vascular cell proliferation. Am J Respir Cell Mol Biol. 2012 Nov;47(5):718-26.
[3] Gray SP, Di Marco E, Okabe J, Szyndralewiez C, Heitz F, Montezano AC, de Haan JB, Koulis C, El-Osta A, Andrews KL, Chin-Dusting JP, Touyz RM, Wingler K, Cooper ME, Schmidt HH, Jandeleit-Dahm KA. NADPH oxidase 1 plays a key role in diabetes mellitus-accelerated atherosclerosis. Circulation. 2013 May 7;127(18):1888-902.
[4] Zhao QD, Viswanadhapalli S2, Williams P2, Shi Q2, Tan C2, Yi X2, Bhandari B2, Abboud HE2. NADPH oxidase 4 induces cardiac fibrosis and hypertrophy through activating Akt/mTOR and NFκB signaling pathways. Circulation. 2015 Feb 17;131(7):643-55.
- 1. Wei Wang, Xiaolong Liang, et al. "NOX4 blockade suppresses titanium nanoparticle-induced bone destruction via activation of the Nrf2 signaling pathway." J Nanobiotechnology. 2022 May 23;20(1):241. PMID: 35606794
- 2. Jiao N, Chen Y, et al. "Protective effects of catalpol on diabetes mellitus-induced male reproductive damage via suppression of the AGEs/RAGE/Nox4 signaling pathway." Life Sci. 2019 Aug 6:116736. PMID: 31398417
- 3. Dª María Castejón Griñán. "MELANOCORTIN 1 RECEPTOR AS REGULATOR OF PROTECTIVE RESPONSES AGAINST OXIDATIVE STRESS AND UVR-INDUCED DNA DAMAGE." UNIVERSIDAD DE MURCIA. 2019.
- 4. Han Z, Kang D, et al. "TGF-β downregulation-induced cancer cell death is finely regulated by the SAPK signaling cascade." Exp Mol Med. 2018 Dec 6;50(12):162. PMID: 30523245
Storage | Store at -20°C |
M.Wt | 394.85 |
Cas No. | 1218942-37-0 |
Formula | C21H19ClN4O2 |
Solubility | ≥39.5 mg/mL in DMSO; insoluble in H2O; ≥2.96 mg/mL in EtOH with gentle warming and ultrasonic |
Chemical Name | 2-(2-chlorophenyl)-4-(3-(dimethylamino)phenyl)-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione |
SDF | Download SDF |
Canonical SMILES | CN(C1=CC=CC(C2=C(C3=O)C(NN3C4=CC=CC=C4Cl)=CC(N2C)=O)=C1)C |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验 [1]: | |
细胞系 |
HPAEC和HPASMC单层细胞,肺动脉内皮细胞 |
溶解方法 |
可溶于DMSO。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。 |
反应条件 |
0.1–20 μM,24小时 |
应用 |
GKT137831(5 μM,20 μM)减弱缺氧诱导的HPAECs和HPASMCs增殖。在HPAECs和HPASMCs中,GKT137831(20 μM)减少缺氧诱导的H2O2产生。在为期72小时的缺氧暴露期间,GKT137831在最后24小时的给药期间减弱了低氧诱导的HPAEC和HPASMCP中PPARγ表达的降低。 |
动物实验 [1-3]: | |
动物模型 |
暴露于常氧或缺氧条件下3周的C57Bl/6小鼠,野生型(WT)和SOD1G37R突变体C57BL/6J小鼠,糖尿病载脂蛋白E缺陷型小鼠 |
给药剂量 |
口服,30或60 mg/kg/d,每天给药,持续10天 |
应用 |
GKT137831(30或60 mg/kg/d)减弱慢性缺氧诱导的右心室肥大、肺血管重塑、血管壁厚度和增殖增加。GKT137831减弱缺氧诱导的PPARγ减少以及TGF-β1表达增加。在WT和SOD1突变小鼠中,GKT137831(60 mg/kg胃内注射)阻断肝纤维化和下调氧化应激、炎症和纤维化的标志物。在糖尿病载脂蛋白E缺陷小鼠中,口服GKT137831(60 mg/kg/d)减轻了糖尿病加速的动脉粥样硬化。 |
注意事项 |
由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。 |
References: [1]. Green D E, Murphy T C, Kang B Y, et al. The Nox4 inhibitor GKT137831 attenuates hypoxia-induced pulmonary vascular cell proliferation[J]. American journal of respiratory cell and molecular biology, 2012, 47(5): 718-726. [2]. Aoyama T, Paik Y H, Watanabe S, et al. Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent[J]. Hepatology, 2012, 56(6): 2316-2327. [3]. Gray SP1, Di Marco E, Okabe J, Szyndralewiez C, et al. NADPH oxidase 1 plays a key role in diabetes mellitus-accelerated atherosclerosis. Circulation. 2013 May 7;127(18):1888-902. |
质量控制和MSDS
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